ArticleCancer discovery2023
Osimertinib + Savolitinib to Overcome Acquired MET-Mediated Resistance in Epidermal Growth Factor Receptor-Mutated, MET-Amplified Non-Small Cell Lung Cancer: TATTON.
Article in Cancer discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02143466 (A Multi-arm, Phase Ib, Open-Label, Multicentre Study to Assess the Safety,Tolerability, Pharmacokinetics and Preliminary Anti-tumour Activity of AZD9291 in Combination With Ascending Doses of Novel Therapeutics in Patients With EGFRm+ Advanced NSCLC Who Have Progressed Following Therapy With an EGFR TKI), which is not on this map. Cited by 121 papers, 4 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Multi-arm, Phase Ib, Open-Label, Multicentre Study to Assess the Safety,Tolerability, Pharmacokinetics and Preliminary Anti-tumour Activity of AZD9291 in Combination With Ascending Doses of Novel Therapeutics in Patients With EGFRm+ Advanced NSCLC Who Have Progressed Following Therapy With an EGFR TKI (TATTON).
Who cites it
121 citing papers in PubMed, 4 syntheses or guidelines pooled it, 146 citations in OpenAlex.
- The prognostic role of circulating DNA markers in patients with lung malignancies: a systematic review and meta-analysis.Biomarkers in medicine · 2025Pooled it
- Pooled it
- [Clinical Practice Guidelines for the Management of Brain Metastases from Non-small Cell Lung Cancer with Actionable Gene Alterations in China (2025 Edition)].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025Guideline
- Efficacy and safety of tyrosine kinase inhibitors with thoracic radiotherapy for patients with oncogene-mutated non-small cell lung cancer: a meta-analysis.Radiation oncology (London, England) · 2024Pooled it
- Genomic Profiling of Epidermal Growth Factor Receptor Mutation-Positive Non-Small Cell Lung Cancer after Progression on First-line Osimertinib: Phase II ORCHARD Study.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Trial
- Population Pharmacokinetics and Exposure-Response Analyses of Savolitinib Alone or in Combination With Osimertinib in Patients With Locally Advanced or Metastatic Solid Tumors.Clinical and translational science · 2026Trial
- Osimertinib with or without savolitinib as first-line treatment for MET-aberrant, EGFR-mutant NSCLC: randomized phase 2 trial (FLOWERS).Nature communications · 2026Trial
- A prospective, multicenter, comprehensive genomic profile signature study in patients with EGFR-mutant advanced non-small cell lung cancer at the first-line treatment failure of osimertinib.Signal transduction and targeted therapy · 2025Trial
- The efficacy and safety of chemo-free therapy in epidermal growth factor receptor tyrosine kinase inhibitor-resistant advanced non-small cell lung cancer: A single-arm, phase II study.Cancer medicine · 2023Trial
- Evaluating the Impact of CYP1A2 Inhibition on the Pharmacokinetics of Savolitinib: A Phase 1 Open-Label Study.Pharmacology research & perspectives · 2026Article
- Promising benefits of MET inhibition combined with EGFR/ALK tyrosine kinase inhibitor in heavily treated non-small cell lung cancer patients withTranslational lung cancer research · 2026Article
- The Pan-Tumor Landscape of Gene Amplifications and Copy Number Amplification Ratio for Established and Emerging Clinical Targets.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- MET Dependence Oversteps EGFR Dependence via Balancing Dimerization of the Receptor Tyrosine Kinases in Osimertinib-Resistant MET-Amplified, EGFR-Mutated Non-Small Cell Lung Cancer.Thoracic cancer · 2026Article
- Sequential EGFR T790M, MET c.3010C>G-Associated Exon 14 Alteration, and RET-CCDC6 Fusion in EGFR-Mutant NSCLC: A Case Report.Thoracic cancer · 2026Article
- Targeting MET in 2025: From Exon 14 Skipping to MET-Amplified Acquired Resistance in Non-Small Cell Lung Cancer.International journal of molecular sciences · 2026Review
- [Chinese Expert Consensus on Diagnosis and Treatment of Non-small Cell Lung Cancer with MET Abnormality (2026 Version)].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Review
- ALK-tyrosine kinase inhibitor resistance due to acquiredTranslational lung cancer research · 2026Article
- Epidermal growth factor receptor tyrosine kinase inhibitor for the treatment of non-small cell lung cancer in the past 30 years (1997-2026).Chinese medical journal · 2026Review
- Durvalumab Plus Chemotherapy in Patients WithJTO clinical and research reports · 2026Article
- First Line and Treatment Sequencing in EGFR-Mutated Metastatic NSCLC: What is Right for Which Patient?Drugs · 2026Review
61 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 15 institutions in 10 countries.
Funding
Abstract
MET-inhibitor and EGFR tyrosine kinase inhibitor (EGFR-TKI) combination therapy could overcome acquired MET-mediated osimertinib resistance. We present the final phase Ib TATTON (NCT02143466) analysis (Part B, n = 138/Part D, n = 42) assessing oral savolitinib 600 mg/300 mg once daily (q.d.) + osimertinib 80 mg q.d. in patients with MET-amplified, EGFR-mutated (EGFRm) advanced non-small cell lung cancer (NSCLC) and progression on prior EGFR-TKI. An acceptable safety profile was observed. In Parts B and D, respectively, objective response rates were 33% to 67% and 62%, and median progression-free survival (PFS) was 5.5 to 11.1 months and 9.0 months. Increased antitumor activity may occur with MET copy number ≥10. EGFRm circulating tumor DNA clearance on treatment predicted longer PFS in patients with detectable baseline ctDNA, while acquired resistance mechanisms to osimertinib + savolitinib were mediated by MET, EGFR, or KRAS alterations. SIGNIFICANCE: The savolitinib + osimertinib combination represents a promising therapy in patients with MET-amplified/overexpressed, EGFRm advanced NSCLC with disease progression on a prior EGFR-TKI. Acquired resistance mechanisms to this combination include those via MET, EGFR, and KRAS. On-treatment ctDNA dynamics can predict clinical outcomes and may provide an opportunity to inform earlier decision-making. This article is highlighted in the In This Issue feature, p. 1.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.